Heart grafts tolerized through third-party multipotent adult progenitor cells can be retransplanted to secondary hosts with no Immunosuppression
Multipotent adult progenitor cells (MAPCs) are an adherent stem cell population that belongs to the mesenchymal-type progenitor cell family. Although MAPCs are emerging as candidate agents for immunomodulation after solid organ transplantation, their value requires further validation in a clinically relevant cell therapy model using an organ donor- and organ recipient-independent, thirdparty cell product. We report that stable allograft survival can be achieved following third-party MAPC infusion in a rat model of fully allogeneic, heterotopic heart transplantation. Furthermore, long-term accepted heart grafts recovered from MAPC-treated animals can be successfully retransplanted to naïve animals without additional immunosuppression. This prolongation of MAPC-mediated allograft acceptance depends upon a myeloid cell population since depletion of macrophages by clodronate abrogates the tolerogenic MAPC effect. We also show that MAPC-mediated allograft acceptance differs mechanistically from drug-induced tolerance regarding marker gene expression, T regulatory cell induction, retransplantability, and macrophage dependence. MAPC-based immunomodulation represents a promising pathway for clinical immunotherapy that has led us to initiate a phase I clinical trial for testing safety and feasibility of third-party MAPC therapy after liver transplantation.
|Keywords||Immunosuppression, Mesenchymal stem cells, T cells, Transplantation|
|Persistent URL||dx.doi.org/10.5966/sctm.2012-0166, hdl.handle.net/1765/75193|
|Journal||Stem Cells Translational Medicine|
Eggenhofer, E, Popp, F, Mendicino, A, Silber, P, Van'T Hof, W, Renner, P, … Dahlke, M.H. (2013). Heart grafts tolerized through third-party multipotent adult progenitor cells can be retransplanted to secondary hosts with no Immunosuppression. Stem Cells Translational Medicine, 2(8), 595–606. doi:10.5966/sctm.2012-0166